The Study of Exenatide Action on Vessel Function in Type 2 Diabetes and Prediabetes
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|ClinicalTrials.gov Identifier: NCT01181986|
Recruitment Status : Completed
First Posted : August 16, 2010
Results First Posted : April 28, 2014
Last Update Posted : May 20, 2014
|Condition or disease||Intervention/treatment||Phase|
|Type 2 Diabetes Mellitus||Drug: Exenatide SC Drug: Exenatide IV Drug: Placebo SC Drug: Exendin-9 Drug: Placebo IV||Phase 4|
Two independent, double-blinded, crossover substudies will be conducted to test the effect of exenatide on daylong post-meal and fasting endothelial function. We will measure endothelial function measured by peripheral arterial tonometry (EndoPAT2000, Itamar Inc.). Patients with recent onset (<3 years) or established (>5 years, Substudy 1 only) diabetes and impaired sugar tolerance (Substudy 2 only) will be studied. The plan is to complete studies in 75 patients (40 in Substudy 1 and 35 in Substudy 2).
In Substudy 1 patients will get twice a day a skin injection of exenatide (Byetta) or identically looking placebo for 10 days, separated by 14-day period. On the next day after each treatemnt period (day 11), they get just one injection and eat a fat-enriched breakfast. A fatty lunch of similar caloric content will be given 4 hours following the breakfast. Endothelial function will be measured just prior to the injection and every 2 hours for total 8 hours.
In Substudy 2, patients on 3 different days will get infusion of exenatide withg or without a blocking drug exendin-9, and a control test with placebo without exendin-9. Endothelial function will be measured before the infusion and 2 hours later during the final 15 minutes of the infusion cocktails. Patients will not eat any meal during the test visits.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||76 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Primary Purpose:||Basic Science|
|Official Title:||Exenatide and Postprandial Endothelial Dysfunction: Effects and Mechanisms|
|Study Start Date :||August 2010|
|Actual Primary Completion Date :||December 2012|
|Actual Study Completion Date :||December 2012|
Experimental: Exenatide SC (Sub-study 1)
Study groups will be individuals with recent onset (<3 years) or established (>5 years) T2D. The plan is to achieve 40 complete studies of subcutaneous injection of exenatide BID (Byetta®, 5 or 10 µg) or identically looking Placebo SC for 10 days, separated by 14-day washout period. On the next day after each treatment phase, a single dose of the assigned medication will be injected just before a fat-enriched breakfast meal. A lunch meal of similar caloric and nutrient content will be administered 4 hours following the breakfast meal. Endothelial function will be measured just prior to the injection and every 2 hours during 8-hour post-breakfast period.
Drug: Exenatide SC
Exenatide 5-10 ug sc BID/10 days
Other Name: Byetta, exendin-4
Drug: Placebo SC
Placebo sc BID/10days
Other Name: placebo
Experimental: Exenatide IV (Sub-study 2)
Study group will be individuals with recent onset (<1 year) T2D on diet and impaired glucose tolerance. The plan is to achieve 35 complete studies. The intervention will include 3 randomly ordered visits with intravenous infusion of exenatide in the presence (v1) or absence (v2) of GLP-1 receptor inhibitor exendin-9, and a control test with Placebo IV without exendin-9 (v3). Endothelial function will be measured at baseline and 2 hours later during the final 15 minutes of the infusion cocktails. Study participants will remain fasting during the test visit (3 hours total).
Drug: Exenatide IV
50 ng/min intravenously for 45 minutes on 2 out of 3 study visits separated by 5-10 days
Other Name: exendin-4, Byetta
Primed (6,000 pM/kg), continuous (600 pM/kg) intravenous infusion for 75 minutes on 1 out of 3 study visits.
Other Name: exendin-(9-39)
Drug: Placebo IV
Intravenous infusion for 45 minutes on 1 out of 3 visits
Other Name: placebo
- Reactive Hyperemia Index (RHI) [ Time Frame: 0, 2, 4, 6 and 8 hours on Day 11 (Sub-study 1); 0 and 120 minutes on test Days 1, 2 & 3 (Sub-study 2) ]Greater RHI reflects greater endothelial function. It is calculated as average post-ischemia pulse magnitude divided by average pre-ischemia pulse magnitude. Results are expressed as least-square means of ANCOVA models.
- Plasma Triglycerides [ Time Frame: 0, 2, 4, 6 and 8 hours post-study drug on day 11 ]Triglycerides concentrations were measured before and 2, 4, 6 and 8 hours following study drug. Results are expressed as least-square means of ANCOVA models adjusted for sampling time and intervention sequence.
- Plasma Glucose [ Time Frame: 0, 2, 4, 6, and 8 hours post-study drug on day 11 ]Plasma glucose was measured before and 2, 4, 6 and 8 hours following study drug administration. Results are expressed as least-square means of ANCOVA models adjusted for sampling time and intervention sequence.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01181986
|United States, Arizona|
|Phoenix VA Medical Center|
|Phoenix, Arizona, United States, 85012|
|Principal Investigator:||Juraj Koska, MD, PhD||Phoenix VA Healthcare System|